Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Azacitidine Plus Phenylbutyrate in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Treatment

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	JHOC-99120302 JHOC-J9982, NCI-270, NCT00005639, 270

Special Category: SPORE trial

Objectives

1. Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with refractory solid tumors.
2. Determine the maximum tolerated dose of this treatment regimen where maximal gene reexpression occurs in these patients.
3. Evaluate the pharmacokinetics of these drugs in these patients.
4. Determine the minimally effective dose of azacitidine in combination with phenylbutyrate that elicits a biological or clinical response in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy
  • Lymphoma allowed
• Progressive disease
• Evaluable disease
• No CNS metastases by CT scan or MRI

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior adjuvant chemotherapy for advanced or metastatic disease and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 8 g/dL (may be achieved by transfusion)
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 2 mg/dL (unless due to hemolysis or Gilbert's syndrome)
• SGOT and SGPT less than 2 times upper limit of normal

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• No active infection
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 2 weeks before, during, and 3 months after study participation

Expected Enrollment

Approximately 3-50 patients will be accrued for this study within 12-18 months.

Outline

This is a dose escalation study.

Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine and phenylbutyrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Michael Carducci, MD, Protocol chair		Ph: 410-614-3977 Email: carducci@welchlink.welch.jhu.edu

Registry Information
Official Title		A Phase I Dose Escalation to Maximally Tolerated Dose Trial of 5-Azacytidine (5 AC, NSC 102816) in Combination with Sodium Phenylbutyrate (PB, NSC 657802) in Patients with Refractory Solid Tumors
Trial Start Date		2000-06-27
Registered in ClinicalTrials.gov		NCT00005639
Date Submitted to PDQ		2000-03-17
Information Last Verified		2005-12-06
NCI Grant/Contract Number		CA06973, CA75525, CA70095, CA58236

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